Proto-oncogenes and tumor suppressor genes represent a cohort of cellular genes which are known to play central roles in the normal growth and proliferation of vertebrate cells. Increasing evidence indicates that alterations in these genes play a role in the induction and/or maintenance of many if not all human malignancies. The purpose of this program is to continue work ongoing over the past eight years to identify and characterize alterations in these genes in a variety of human malignancies. The program is designed to screen human tumor tissues using nucleic acid and antibody probes for genes Of interest to detect patterns of alterations in various groups of malignancies. As a result of this approach the program has been effective in identifying proto-oncogene alterations which may be important in the pathogenesis of human breast and ovarian cancers and has used this information as well as information generated by other laboratories to generate reagents to study the role these alterations play on the biology of the diseases in which they occur. We propose to use these studies to gain new insights into the diagnosis, prognosis and treatment of human malignancies.